Restless leg syndrome (RLS) is a common sleep disorder characterized by unpleasant sensations in the lower limbs that occur at rest and are relieved by movement. Several studies have reported familial aggregation of RLS and have frequently suggested that it segregates as an autosomal dominant trait, with a recurrence risk among first-degree relatives of RLS probands as high as 40 percent. RLS patients with a positive family history have a tendency to an earlier age of onset, which also suggests an important genetic component in the etiology of RLS. Our hypothesis is that at least part of the observed familial aggregation seen in RLS is due to genetic factors. Our goal is to map the gene (or genes) that predispose to familial RLS using subjects from a homogeneous population with a founder effect where RLS prevalence rates have been shown to be increased. In addition, we will replicate positive findings in independent samples from French-Canadian and panmixed populations, and subsequently, identify the gene (or genes). Specifically, we will: (1) Collect unrelated French-Canadian patients and families of probands affected with RLS defined according to stringent criteria; (2) Collect RLS families from panmixed populations; (3) Conduct a systematic scan of the whole human genome in French-Canadian families using traditional lod score and nonparametric linkage analysis in order to identify loci that may be implicated in the etiology of RLS; (4) Replicate the positive findings using two different samples: a) unrelated RLS patients of French-Canadian origin, and b) a collection of large and nuclear families from panmixed populations; (5) Identify the RLS gene. In addition to better define the disease, the identification of a gene that contributes to the etiology of RLS may lead to new insights into the mechanisms of the sleep processes and episodic movements. Furthermore, finding a predisposing gene may lead to improved treatment of RLS and related conditions. The proposed investigation will be carried out in a three year period.